Chiral hypervalent iodine-catalyzed enantioselective oxidative Kita spirolactonization of 1-naphthol derivatives and one-pot diastereo-selective oxidation to epoxyspirolactones

Tetrahedron 66 (2010) 5841e5851

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Chiral hypervalent iodine-catalyzed enantioselective oxidative Kita spirolactonization of 1-naphthol derivatives and one-pot diastereo-selective oxidation to epoxyspirolactones Muhammet Uyanik a, Takeshi Yasui a, Kazuaki Ishihara a, b, * a b

Graduate School of Engineering, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8603, Japan Japan Science and Technology Agency (JST), CREST, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, Japan

a r t i c l e i n f o

a b s t r a c t

Article history: Received 15 March 2010 Received in revised form 13 April 2010 Accepted 13 April 2010 Available online 18 April 2010

We demonstrate here the rational design of a conformationally flexible C2-symmetric iodosylarene 8g based on secondary nes* or hydrogen-bonding interactions as a chiral catalyst for the enantioselective Kita oxidative spirolactonization of 1-naphthol derivatives 5. Iodosylarenes 8 were generated in situ from iodoarenes 7 and mCPBA as a co-oxidant. Furthermore, epoxyspirolactone 15 was obtained by the onepot oxidation of 5 with mCBPA in the presence of 7g. Thus, the enantioselective oxidation of 5 to 6 and the successive enantio- and diastereo-selective oxidation of 5 to 15 proceeded in good yields when we controlled the amount of mCPBA. Ó 2010 Elsevier Ltd. All rights reserved.

Keywords: Hypervalent iodine Asymmetric oxidation Dearomatization Spirolactone

1. Introduction Over the past two decades, hypervalent iodine compounds have been the focus of great attention due to their mild and chemoselective oxidizing properties and the fact that they are environmentally benign compared to toxic metal reagents.1 However, the stoichiometric use of hypervalent iodine compounds has been limited because of their potentially shock-sensitive explosiveness and/or poor solubility in common organic solvents.1 Thus, the development of hypervalent iodine-catalyzed oxidation reactions with co-oxidants is needed.1,2 In particular, the development of chiral hypervalent iodine-catalyzed enantioselective oxidative coupling reactions is one of the most challenging areas in asymmetric organocatalysis.3,4 There are some examples of in situgenerated chiral iodosylarene(I(III)) or iodylarene(I(V)) catalysis with meta-chloroperbenzoic acid (mCPBA)5 as a co-oxidant (Fig. 1).4 Wirth and co-workers reported the enantioselective a-oxysulfonylation of ketones with 1 as a precatalyst.4a Quideau and coworkers reported the enantioselective hydroxylative dearomatization of 2-methyl-1-naphthol with 2 as a precatalyst.4b However, the enantioselectivity has been modest. Recently, Kita and coworkers reported the enantioselective oxidative dearomatization of

* Corresponding author. Tel.: þ81 52 7893331; fax: þ81 52 7893222; e-mail address: [email protected] (K. Ishihara). 0040-4020/$ e see front matter Ó 2010 Elsevier Ltd. All rights reserved. doi:10.1016/j.tet.2010.04.060

Figure 1. Chiral iodoarene precatalysts 1e3 and iodosylarene 4.

1-naphthol derivatives 5 to spirolactones 6 with high enantioselectivities (up to 86% ee) using stoichiometric chiral iodine(III) reagent 4, which has a conformationally rigid 1,1-spiroindanone backbone (Scheme 1).6 They also succeeded in the catalytic use of 4 (30 mol % based on iodine) that was generated in situ from 3 and mCPBA in the presence of acetic acid, although the enantioselectivity was reduced to 69% ee (Scheme 1).6

Scheme 1. Enantioselective oxidative spirolactonization of 1-naphthols (5) reported by Kita and co-workers.6

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Very recently, we reported conformationally flexible C2-symmetric chiral iodoarenes 7g as a highly effective precatalyst for the enantioselective Kita oxidative spirolactonization (Scheme 2).7 In this report, we described a detailed investigation of enantioselective oxidative spirolactonization. A broad range of substrates and higher enantioselectivities of up to 92% ee were achieved using iodosylarene 8g generated in situ from 7g and mCPBA. To the best of our knowledge, the present catalysis provides the highest asymmetric induction among previous chiral hypervalent iodine-catalyzed enantioselective oxidative reactions.3,4,6 Furthermore, we briefly highlight here the synthetic utility of the present oxidation. The selective oxidation of 5 to spirolactones 6 and the successive oxidation of 5 to epoxyspirolactones 15 proceeded in good yields when we controlled the amount of mCPBA. Scheme 4. Synthesis of chiral iodoarenes 7 and 11.

The starting materials 5 used in this study were prepared in good yields in three steps from readily available 1-napthols 12 (Scheme 5).6b Treatment of 12 with triethyl orthoacrylate in the presence of pivalic acid afforded diethoxychromane 13.10 Acid hydrolysis of 13 furnished dihydrocoumarin, which was transformed to 5 by hydrolysis.

Scheme 2. In situ-generated 8g-catalyzed enantioselective oxidative spirolactonization of 5 with mCPBA.7

2. Results and discussion C2-Symmetric chiral iodoarenes 7 consist of three units, including an iodoaryl moiety (A), chiral linkers (B), and subfunctional groups (C) (Scheme 3). These units can be easily combined to give a wide variety of chiral iodoarenes 7. The iodosylarenes 8 generated in situ from iodoarenes 7 were expected to exhibit intramolecular nes* interactions between the electron-deficient iodine(III) center (CeI s* orbital) of A and the Lewis-basic group of C (lone pair n), such as carbonyl groups (8-I).1,8 Alternatively, intramolecular hydrogen-bonding interactions between the acidic hydrogen of C (COYeH) and the ligand (L, such as an acetoxy group) of iodine(III) might also be generated (8-II). We envisioned that a suitable chiral environment might be constructed around the iodine(III) center of 8 via such intramolecular interactions.

Scheme 3. Design of conformationally flexible iodoarenes 7 (precatalyst) and iodosylarenes 8 (catalyst).

Chiral iodoarenes 7 were easily prepared in two or three steps from 2-iodoresorcinol (Scheme 4). The Mitsunobu reaction of 2iodoresorcinol (9, R1¼H)9 with ()-ethyl lactate (10, R2¼Me) gave C2-symmetric chiral iodoarene 7a in 90% yield. Hydrolysis of 7a gave 7b quantitatively without epimerization. Treatment of 7b with thionyl chloride followed by several amines gave the corresponding amides 7cei in good yields. 7jel, 11a,3g and 11b were also prepared in a similar manner.

Scheme 5. Synthesis of 1-naphthol derivatives 5.

The chiral iodoarenes 7 were examined for use as precatalysts for the enantioselective oxidative spirolactonization of 5a to spirolactone 6a in the presence of mCPBA as a co-oxidant under Kita’s conditions (Table 1).6 The use of diester 7a and Table 1 Precatalyst screening for the oxidative spirolactonization of 5aa

Entry

Precat. 7 or 11

Yieldb (%)

eec (%)

1 2 3 4 5 6 7 8 9 10 11 12 13 14

7a 7b 7c 7d 7e 7f 7g 7h 7i 7j 7k 7l 11a 11b

27 26 40 25 53 36 64 37 39 37 47 70 24 42

23 43 70 77 75 84 82 51 52 50 80 83 13 32

a The reactions were performed with 0.05 mmol of 5a and 1.3 equiv of mCPBA in the presence of 7 or 11 (15 mol %). b Isolated yield of 6a by column chromatography is shown. c The ee values of 6a were determined by chiral stationary phase HPLC.

M. Uyanik et al. / Tetrahedron 66 (2010) 5841e5851

dicarboxylic acid 7b gave (þ)-6a with 23% ee and 43% ee, respectively (entries 1 and 2). In contrast, the use of bis(primary amide) 7c gave (þ)-6a with 70% ee (entry 3), and the use of bis (N-aryl amide)s 7deg further increased the enantioselectivity (entries 4e7). Bis(N-mesityl amide) 7g was the best precatalyst with respect to activity and enantioselectivity (entry 7, 64% yield, 82% ee). The use of tertiary amides, such as 7h and 7i gave moderate enantioselectivities (entries 8 and 9). Bis(Nmesityl amide) 7j bearing a methyl group at the para-position of the iodoaryl moiety (A) gave modest enantioselectivity (entry 10). In contrast, the use of F-substituted 7k gave (þ)-6a with 80% ee (entry 11). Bis(N-mesityl amide) 7l bearing an iPr group on the chiral linker (B) also gave high enantioselectivity and high catalytic activity as well as 5g (entry 12). Meanwhile, C2unsymmetrical iodoarenes, such as monoester 11a3g and mono (N-mesityl amide) 11b gave low enantioselectivities (entries 13 and 14). Thus, the C2-symmetric chirality in 8 was essential for the present enantioselective oxidative spirolactonization. Next, we optimized the reaction conditions with 7g (Table 2). Enantioselectivity was enhanced at lower temperatures and under diluted conditions (entries 2 and 3). The highest enantioselectivity (92% ee) was observed in chloroform (entries 5 and 6). Notably, high or good enantioselectivities were observed regardless of the polarity of the solvent (entries 5e12). In particular, (þ)-6a was obtained in 82% yield with 85% ee in nitromethane (entry 9). In contrast, almost no reaction occurred when the reaction was performed in tetrahydrofuran or diethyl ether (entries 13 and 14). Table 2 Optimization of the reaction conditionsa

Entry

Solvent

Conditions

Yieldb (%)

eec (%)

1 2 3 4 5e 6 7 8 9 10 11 12 13 14 15

CH2Cl2d CH2Cl2 CH2Cl2 CH2Cl2 CHCl3 CHCl3 Toluene CH3CN CH3NO2 EtOAc CF3CH2OH (CF3)2CHOH THF Et2O CHCl3eCH3NO2f

0  C, 3 h 0  C, 5 h 20  C, 48 h 25  C, 5 h 0  C, 18 h 20  C, 48 h 0  C, 5 h 0  C, 5 h 0  C, 5 h 0  C, 5 h 0  C, 5 h 0  C, 5 h 0  C, 5 h 0  C, 5 h 0  C, 5 h

64 56 75 70 60 55 46 23 82 14 66 63 <5 <5 65

82 88 90 83 92 92 77 83 85 81 70 41 n.d. n.d. 90

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Table 3 Scope and limitations of the spirolactonization reactiona

Entry 1 2 3 4 5 6 7 8 9 10

6

Conditions

(þ)-6b (þ)-6c (þ)-6d (þ)-6e (R)-()-6f ()-6g ()-6h (þ)-6i (þ)-6j (þ)-6k

d

CHCl3eCH3NO2, CHCl3, 30 h CHCl3, 16 h CHCl3, 27 h CHCl3eCH3NO2,d CHCl3, 30 h CHCl3eCH3NO2,d CHCl3eCH3NO2,d CHCl3eCH3NO2,d CHCl3, 18 h

17 h

16 h 7h 18 h 24 h

Yieldb (%)

eec (%)

59 72 67 62 94 88 28 40 3 53

84 90 85 (98) 87 (98) 83 (>99) 91 0 87 88 91

a The reactions were performed with 0.05 mmol of 5 and 1.2e1.5 equiv of mCPBA in the presence of 7g (10 mol %). b Isolated yield of 6 by column chromatography is shown. c The ee values of 6 were determined by chiral stationary phase HPLC. Ee value in parentheses is that obtained after single recrystallization. d Reaction was performed in CHCl3eCH3NO2 (2/1, v/v) mixed solvents.

recrystallization (98% ee, entries 3e5).11 The absolute stereochemistry of ()-6f was determined to be (R) based on the X-ray crystal analysis (>99% ee, entry 5, Fig. 2). Notably, the oxidation of 4-benzoylnaphthol derivative 5f gave 6f in 94% yield with 83% ee (entry 5). In sharp contrast, according to Kita’s report, 4 gave racemic 6f.6b Although the oxidation of 4methoxynaphthol derivative 5h gave racemic 6h (entry 8), as did Kita’s reagent 4,6 7g gave (þ)-6i with 87% ee, for the oxidation of 6-methoxynaphthol derivative 5i (entry 8). Unfortunately, 3-methoxynaphthol derivative 5j gave (þ)-6j in very low yield (entry 9). Notably, the oxidation of 3-benzyloxymethyl-substituted 5k gave (þ)-6k in good yield with 91% ee (entry 10). Analogs of 6k may become new chiral intermediate candidates in enantioselective total syntheses of Lactonamycin.12

a Unless otherwise noted, the reactions were performed with 0.05 mmol of 5a and 1.3 equiv of mCPBA in the presence of 7g (15 mol %). b Isolated yield of 6a by column chromatography is shown. c The ee values of 6a were determined by chiral stationary phase HPLC. d Reaction was performed in CH2Cl2 (0.5 mL, 0.2 M). e The reaction was performed with 1.0 mmol of 5a and 1.2 equiv of mCPBA. f Reaction was performed in CHCl3eCH3NO2 (2/1, v/v, 0.02 M) mixed solvents.

To explore the generality and substrate scope of the present spirolactonization, several 1-naphthol derivatives 5 were examined as substrates under optimized conditions using 7g (10 mol %) and mCPBA (1.2e1.5 equiv) (Table 3). The oxidation of 4-substituted naphthol derivatives 5beg gave the corresponding spirolactones 6beg in good to high yields with high enantioselectivities (entries 1e6). Fortunately, nearly enantiomerically pure 6def were obtained after a single

Figure 2. ORTEP drawing of (R)-()-6f (>99% ee).

Iodosylarene diacetate 14, which was analogous to 8g, was isolated through the oxidation of 7g with Selectfluor.6 Treatment of 5a with 1 equiv of 14 in dichloromethane at 0  C gave (þ)-6a with 85% ee (Scheme 6 and entry 1 in Table 2). Thus, iodine(III) generated in situ from 7 should be the actual oxidant species for the present catalytic oxidation.

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Scheme 6. Preparation of iodosylarene 14 from 7g and the oxidation of 5a with 14.

Next, stoichiometric oxidations of 5 with 1 equiv of 14 were investigated under optimal conditions (Table 4). The oxidation of 5a, 5b, 5i, and 5k gave corresponding spirolactone (þ)-6 in high yields and with high enantioselectivities (entries 1e3 and 5). Furthermore, (þ)-6j was obtained in 87% yield with 95% ee for the stoichiometric oxidation of 5j (entry 4). Table 4 Stoichiometric oxidation of 5 with iodosylarene 14a

Entry

6

Yieldb (%)

eec (%)

1 2 3 4 5

(þ)-6a (þ)-6b (þ)-6i (þ)-6j (þ)-6k

70 85 89 87 75

90 89 90 95 94

a b c

Scheme 8. Epoxidation of (þ)-6a to epoxyspirolactone ()-15.

Bromohydrin spirolactone (þ)-17 was obtained in high yield and high diastereoselectivity by treatment of (þ)-6a with NBS in aqueous THF (Scheme 9).16 Treatment of (þ)-17 with K2CO3 gave epoxyspirolactone (þ)-16, which was a diastereomer of ()-15 (Scheme 9). Thus, both of the enantioenriched epoxyspirolactones ()-15 and (þ)-16 could be obtained selectively from 6a in good yields (Schemes 8 and 9).

The reactions were performed with 0.05 mmol of 5 and 0.05 mmol of 14. Isolated yield of 6 by column chromatography is shown. The ee values of 6 were determined by chiral stationary phase HPLC.

Oxidation of 5a with 5 equiv of mCPBA in the presence of 10 mol % of 7g gave epoxyspirolactone ()-15 in good yield. (Scheme 7). Enantiomerically pure ()-15 was obtained after

Scheme 9. Conversion of (þ)-6a to bromohydrin spirolactone (þ)-17, and conversion of (þ)-17 to epoxyspirolactone (þ)-16.

3. Conclusion Scheme 7. One-pot oxidation of 5a to epoxyspirolactone ()-15.

a single recrystallization. Thus, the selective oxidation of 5 to spirolactone 6 and the successive enantio- and diastereo-selective oxidation of 5 to epoxyspirolactone 15 proceeded in good yields when we controlled the amount of mCPBA.13 The relative stereochemistry of 15 was determined by the X-ray crystal analysis of ()-15 (Fig. 3).

In summary, we have demonstrated the rational design of a conformationally flexible iodosylarene 8g as a chiral catalyst based on secondary nes* or hydrogen-bonding interactions for the enantioselective Kita oxidative spirolactonization. In a similar way, it is likely that several precatalysts for other enantioselective oxidative transformations will be found in the library of 7. Furthermore, we have briefly highlighted the synthetic utility of the present oxidation. Epoxyspirolactone 15 was obtained by the onepot oxidation of 5a with mCPBA in the presence of 7g. Thus, the enantioselective oxidation of 5 to 6 and the successive enantio- and diastereo-selective oxidation of 5 to 15 proceeded in good yields when we controlled the amount of mCPBA. Additionally, unsaturated spirolactones 6 could be easily transformed to epoxyspirolactones 15 and bromohydrin spirolactones 17 in good yields and with high diastereoselectivities. Basic treatment of 17 gave epoxyspirolactone 16, which is diastereomer of 15. Thus, both of the enantioenriched epoxyspirolactones 15 and 16 could be obtained selectively from unsaturated spirolactone 6 in good yields. Studies to elucidate the detailed mechanism of oxidative spirolactonization are currently underway. 4. Experimental section

Figure 3. ORTEP drawing of ()-15.

Epoxyspirolactone ()-15 could also be obtained by the epoxidation of unsaturated spirolactone (þ)-6a with in situ-generated peracetic acid14 or MeReO3eH2O215 in good yield and with higher diastereoselectivity (Scheme 8).

4.1. General methods 1 H NMR spectra were measured on a Varian Gemini-2000 (300 MHz), Varian INOVA-500 (500 MHz) or a JEOL ECS-400 (400 MHz) spectrometer at ambient temperature. Data were recorded as follows: chemical shift in parts per million from

M. Uyanik et al. / Tetrahedron 66 (2010) 5841e5851

internal tetramethylsilane on the d scale, multiplicity (s¼singlet; d¼doublet; t¼triplet; q¼quartet; m¼multiplet), coupling constant (Hz), integration, and assignment. 13C NMR spectra were measured on a Varian Gemini-2000 (75 MHz), Varian INOVA-500 (125 MHz) or JEOL ECS-400 (100 MHz) spectrometers. Chemical shifts were recorded in parts per million from the solvent resonance employed as the internal standard (deuterochloroform at 77.00 ppm). Highperformance liquid chromatography (HPLC) analysis was conducted using Shimadzu LC-10 AD coupled diode array-detector SPD-MA-10A-VP and chiral column of Daicel CHIRALCEL OD-H (4.6 mm25 cm) AD-3 (4.6 mm25 cm). For thin-layer chromatography (TLC) analysis throughout this work, Merck precoated TLC plates (silica gel 60 GF254 0.25 mm) were used. The products were purified by column chromatography on silica gel (E. Merck Art. 9385). In experiments that required dry solvents, tetrahydrofuran (THF), dichloromethane, and toluene were purchased from Wako as the ‘anhydrous’ and stored over 4A molecular sieves. Other solvents were purchased from Aldrich or Wako and used without further purification. Other simple chemicals were analytical-grade and obtained commercially and used without further purification. 4.2. Synthesis of chiral iodoarenes 7ael (Scheme 4) 4.2.1. (2R,20 R)-Diethyl 2,20 -(2-iodo-1,3-phenylene)bis(oxy)dipropanoate (7a). To a solution of 2-iodoresorcinol9 (9, 2.36 g, 10.0 mmol), PPh3 (6.56 g, 25.0 mmol) and ()-lactic acid ethylester (10, 2.80 mL, 25.0 mmol) in THF (50 mL) was added slowly diisopropyl azodicarboxylate (DIAD, 1.9 M in toluene, 25.0 mmol, 13.2 mL) at 0  C. The reaction mixture was allowed to warm to room temperature. After stirring for 6 h, the resulting mixture was concentrated in vacuo. The residue was purified by flash column chromatography on silica gel (eluent: hexaneeEtOAc¼15:1) to give 7a (3.93 g, 9.0 mmol) in 90% yield. Colorless oil; TLC, Rf¼0.33 (hexaneeEtOAc¼4:1); IR (neat) 2985, 1753, 1587, 1461, 1252, 1135 cm1; 1H NMR (CDCl3, 400 MHz) d 1.24 (t, J¼7.2 Hz, 6H), 1.70 (d, J¼6.8 Hz, 6H), 4.18e4.24 (m, 4 h), 4.75 (q, J¼6.8 Hz, 2H), 6.37 (d, J¼8.4 Hz, 2H), 7.13 (t, J¼8.4 Hz, 1H); 13C NMR (CDCl3, 100 MHz) d 14.0 (2C), 18.5 (2C), 61.2 (2C), 74.2 (2C), 80.6, 106.9 (2C), 129.4, 158.2 (2C), 171.6 (2C); HRMS (FABþ) m/z calcd for C16H22IO6 (MþH) 437.0461, found 437.0462; [a]26 D 21.6 (c 1.0, CHCl3). 4.2.2. (2R,20 R)-2,20 -(2-Iodo-1,3-phenylene)bis(oxy)dipropanoic acid (7b). To a solution of 7a (3.93 g, 9.0 mmol) in THF (25.0 mL) and MeOH (25.0 mL) was added 2 M NaOH (25 mL) and stirred overnight at room temperature. The reaction mixture was cooled to 0  C, quenched with 1 M HCl and extracted with EtOAc. The organic layers were dried over anhydrous MgSO4 and the solvents were removed in vacuo to give analytically pure 7b (3.42 g, 9.0 mmol) in >99% yield. White solid; TLC, Rf¼0.15 (hexaneeEtOAceCHCl3¼ 1:2:1 with a few drops of AcOH); IR (KBr) 3600e2700, 2525, 1715, 1581, 1458, 1252 cm1; 1H NMR (DMSO-d6, 400 MHz) d 1.54 (d, J¼6.8 Hz, 6H), 4.84 (q, J¼6.8 Hz, 2H), 6.42 (d, J¼8.0 Hz, 2H), 7.21 (t, J¼8.0 Hz, 1H); 13C NMR (DMSO-d6, 100 MHz) d 18.4 (2C), 72.8 (2C), 79.6, 105.9 (2C), 129.7, 157.8 (2C), 172.7 (2C); HRMS (FABþ) m/z calcd for C12H13IO6 (M) 379.9757, found 329.9755; [a]26 D 6.4 (c 1.0, THF). 4.2.3. (2R,20 R)-2,20 -(2-Iodo-1,3-phenylene)bis(oxy)dipropan amide (7c). A solution of 7b (190 mg, 0.50 mmol) in SOCl2 (4.0 mL) was refluxed for 1 h. To the resulting mixture was added benzene (22 mL), and excess reagents were removed in vacuo. The residue was dissolved in CH2Cl2 (5 mL), and to the resulting mixture was added excess NH3 gas with cooling (78  C). The resulting mixture was stirred at 78  C for 2 h, and gradually warmed to room temperature. After stirring for overnight, the reaction mixture was poured into 1 M HCl and extracted with CHCl3. The organic layers were dried over anhydrous MgSO4 and the solvents were removed

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in vacuo. The residue was purified by flash column chromatography on silica gel (eluent: hexaneeEtOAc¼1:2) to give 7c (0.15 g, 0.4 mmol) in 79% yield. White solid; TLC, Rf¼0.13 (hexaneeEtOAceCHCl3¼1:2:1); IR (KBr) 3455, 3398, 3217, 1709, 1460, 1251, 1111 cm1; 1H NMR (DMSO-d6, 400 MHz) d 1.47 (d, J¼6.8 Hz, 6H), 4.68 (q, J¼6.8 Hz, 2H), 6.51 (d, J¼8.0 Hz, 2H), 7.24 (t, J¼8.0 Hz, 1H), 7.30 (s, 2H), 7.42 (s, 2H); 13C NMR (DMSO-d6, 100 MHz) d 18.6 (2C), 74.8 (2C), 80.6, 106.7 (2C), 129.9, 157.5 (2C), 172.9 (2C); HRMS (FABþ) m/z calcd for C12H16IN2O4 (MþH) 379.0155, found 379.0152; [a]26 D 120.9 (c 1.0, CHCl3). 4.2.4. (2R,2 0 R)-2,2 0 -(2-Iodo-1,3-phenylene)bis(oxy)bis(N-phenylpropanamide) (7d). This compound was prepared as 7c from 7b with aniline in 69% yield. White solid; TLC, Rf¼0.37 (hexaneeEtOAc¼1:1); IR (KBr) 3402, 1685, 1600, 1529, 1439, 1242, 1104 cm1; 1H NMR (CDCl3, 400 MHz) d 1.75 (d, J¼6.4 Hz, 6H), 4.96 (q, J¼6.4 Hz, 2H), 6.60 (d, J¼8.4 Hz, 2H), 7.16 (t, J¼8.0 Hz, 2H), 7.33 (t, J¼8.4 Hz, 1H), 7.37 (t, J¼8.0 Hz, 4H), 7.66 (d, J¼8.0 Hz, 4H), 8.79 (br s, 2H); 13C NMR (CDCl3, 100 MHz) d 18.3 (2C), 76.1 (2C), 80.7, 107.2 (2C), 119.8 (4C), 124.7 (2C), 129.1 (4C), 130.8, 137.2 (2C), 156.7 (2C), 168.9 (2C); HRMS (FABþ) m/z calcd for C24H24IN2O4 (MþH) 531.0781, found 531.0794; [a]25 D 229.4 (c 1.0, CHCl3). 4.2.5. (2R,20 R)-2,20 -(2-Iodo-1,3-phenylene)bis(oxy)bis(N-(3,5-bis(trifluoromethyl)phenyl)propanamide) (7e). This compound was prepared as 7c from 7b with 3,5-di-trifluoromethylaniline in 80% yield. White solid; TLC, Rf¼0.57 (hexaneeEtOAc¼1:1); IR (KBr) 3367, 1701, 1543, 1460, 1383, 1279, 1132 cm1; 1H NMR (CDCl3, 400 MHz) d 1.77 (d, J¼6.8 Hz, 6H), 5.00 (q, J¼6.8 Hz, 2H), 6.64 (d, J¼8.4 Hz, 2H), 7.38 (t, J¼8.4 Hz, 2H), 7.67 (s, 2H), 8.17 (s, 4H), 9.03 (br s, 2H); 13C NMR (CDCl3, 100 MHz) d 18.1 (2C), 76.1 (2C), 80.9, 107.6 (2C), 118.1 (2C), 119.5 (4C), 123.0 (d, JCeF¼271 Hz, 4C), 131.1, 132.3 (q, JCeF¼33 Hz, 4C), 138.6 (2C), 156.5 (2C), 169.5 (2C); 19F NMR (CDCl3, 376 MHz) d 62.8; HRMS (FABþ) m/z calcd for C28H20F12IN2O4 (MþH) 803.0276, found 803.0272; [a]26 D 147.3 (c 1.0, CHCl3). 4.2.6. (2R,2 0 R)-2,2 0 -(2-Iodo-1,3-phenylene)bis(oxy)bis(N-(3,5-ditertbutylphenyl)propanamide) (7f). This compound was prepared as 7c from 7b with 3,5-di-tert-butylaniline in 62% yield. White solid; TLC, Rf¼0.64 (hexaneeEtOAc¼1:1); IR (KBr) 3382, 3290, 2962, 1690, 1669, 1457, 1248, 1113 cm1; 1H NMR (CDCl3, 400 MHz) d 1.34 (s, 36H), 1.75 (d, J¼6.8 Hz, 6H), 4.93 (q, J¼6.8 Hz, 2H), 6.62 (d, J¼8.4 Hz, 2H), 7.19 (s, 2H), 7.33 (t, J¼8.4 Hz, 2H), 7.51 (s, 4H), 8.72 (s, 2H); 13C NMR (CDCl3, 100 MHz) d 18.3 (2C), 31.3 (12C), 34.9 (4C), 76.4 (2C), 80.7, 107.2 (2C), 114.4 (4C), 118.9 (2C), 130.8, 136.6 (2C), 151.8 (4C), 156.9 (2C), 168.8 (2C); HRMS (FABþ) m/z calcd for C40H56IN2O4 (MþH) 755.3285, found 755.3277; [a]26 D 180.9 (c 1.0, CHCl3). 4.2.7. (2R,20 R)-2,20 -(2-Iodo-1,3-phenylene)bis(oxy)bis(N-mesitylpropanamide) (7g). This compound was prepared as 7c from 7b with mesitylaniline in 78% yield. White solid; TLC, Rf¼0.42 (hexaneeEtOAc¼1:1); IR (KBr) 3255, 1673, 1528, 1463, 1256, 1138 cm1; 1H NMR (CDCl3, 400 MHz) d 1.77 (d, J¼6.8 Hz, 6H), 2.15 (s, 12H), 2.26 (s, 6H), 5.00 (q, J¼6.8 Hz, 2H), 6.64 (d, J¼8.4 Hz, 2H), 6.86 (s, 4H), 7.34 (t, J¼8.4 Hz, 1H), 8.02 (s, 2H); 13C NMR (CDCl3, 100 MHz) d 18.2 (4C), 18.7 (2C), 20.8 (2C), 76.0 (2C), 80.4, 107.0 (2C), 128.9 (4C), 130.0 (2C), 130.6, 135.0 (4C), 137.1 (2C), 156.9 (2C), 169.6 (2C); HRMS (FABþ) m/z calcd for C30H36IN2O4 (MþH) 615.1720, found 615.1717; [a]26 D 116.1 (c 1.0, CHCl3). 4.2.8. (2R,20 R)-2,20 -(2-Iodo-1,3-phenylene)bis(oxy)bis(1-(pyrrolidin1-yl)propan-1-one) (7h). This compound was prepared as 7c from 7b with pyrrolidine in >99% yield. White solid; TLC, Rf¼0.19 (hexaneeEtOAceCHCl3¼1:2:1); IR (KBr) 2980, 2875, 1650, 1461, 1428, 1255, 1103 cm1; 1H NMR (CDCl3, 400 MHz) d 1.55e1.92 (m,

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8H), 1.68 (d, J¼6.8 Hz, 6H), 3.31 (dt, J¼6.8, 11.2 Hz, 2H), 3.42e3.53 (m, 4H), 3.72 (dt, J¼6.8, 11.2 Hz, 2H), 4.83 (q, J¼6.8 Hz, 2H), 6.46 (d, J¼8.0 Hz, 2H), 7.16 (t, J¼8.0 Hz, 2H); 13C NMR (CDCl3, 100 MHz) d 17.4 (2C), 23.2 (2C), 26.5 (2C), 46.3 (2C), 46.8 (2C), 76.5 (2C), 78.5, 106.0 (2C), 130.3, 157.6 (2C), 169.3; HRMS (FABþ) m/z calcd for C20H28IN2O4 (MþH) 487.1094, found 487.1092; [a]25 D 161.0 (c 1.0, CHCl3). 4.2.9. (2R,20 R)-2,20 -(2-Iodo-1,3-phenylene)bis(oxy)bis(N,N-diphenylpropanamide) (7i). This compound was prepared as 7c from 7b with diphenylamine in 72% yield. White solid; TLC, Rf¼0.37 (hexaneeEtOAc¼1:1); IR (KBr) 3600e3200, 3448, 1686, 1491, 1458, 1247, 1092 cm1; 1H NMR (CDCl3, 400 MHz) d 1.62 (d, J¼6.4 Hz, 6H), 4.88 (q, J¼6.4 Hz, 2H), 6.40 (d, J¼8.4 Hz, 2H), 7.11 (t, J¼8.4 Hz, 2H), 7.20e7.32 (m, 20H); 13C NMR (CDCl3, 75 MHz) d 18.1 (2C), 73.6 (2C), 83.0, 108.8 (2C), 126.1 (m, 8C), 130.0 (m, 13C), 141.0 (m, 2C), 142.0 (m, 2C), 158.0 (2C), 170.5 (2C); HRMS (FABþ) m/z calcd for C36H32IN2O4 (MþH) 683.1407, found 683.1407; [a]26 D 30.8 (c 1.0, CHCl3). 4.2.10. (2R,20 R)-2,20 -(2-Iodo-5-methyl-1,3-phenylene)bis(oxy)bis(Nmesitylpropanamide) (7j). This compound was prepared as 7g from 2-iodo-5-methylresorcinol. White solid; TLC, Rf¼0.56 (hexaneeEtOAceCHCl3¼1:2:1); IR (KBr) 3234, 2918, 1668, 1578, 1508, 1440, 1239, 1108 cm1; 1H NMR (CDCl3, 400 MHz) d 1.77 (d, J¼6.8 Hz, 6H), 2.14 (s, 12H), 2.26 (s, 6H), 2.35 (s, 3H), 4.98 (q, J¼6.8 Hz, 2H), 6.48 (s, 2H), 6.90 (s, 4H), 7.97 (s, 2H); 13C NMR (CDCl3, 100 MHz) d 18.2 (4C), 18.8 (2C), 20.9 (2C), 21.8, 76.0 (2C), 76.2, 108.1 (2C), 129.0 (4C), 130.0 (2C), 135.0 (4C), 137.2 (2C), 141.4, 156.6 (2C), 169.7 (2C); HRMS (FABþ) m/z calcd for C31H38IN2O4 (MþH) 629.1876, found 629.1870; [a]23 D 94.9 (c 1.0, CHCl3). 4.2.11. (2R,20 R)-2,20 -(5-Fluoro-2-iodo-1,3-phenylene)bis(oxy)bis(Nmesitylpropanamide) (7k). This compound was prepared as 7g from 5-fluoro-2-iodoresorcinol. Pale purple solid; TLC, Rf¼0.60 (hexaneeEtOAceCHCl3¼1:2:1); IR (KBr) 3246, 2920, 1668, 1609, 1508, 1431, 1211, 1105 cm1; 1H NMR (CDCl3, 400 MHz) d 1.78 (d, J¼6.8 Hz, 6H), 2.16 (s, 12H), 2.27 (s, 6H), 4.94 (q, J¼6.8 Hz, 2H), 6.46 (d, J¼10.1 Hz, 2H), 6.91 (s, 4H), 7.94 (s, 2H); 13C NMR (CDCl3, 100 MHz) d 18.3 (4C), 18.6 (2C), 20.9 (2C), 73.5, 76.4 (2C), 95.4 (d, JCeF¼27 Hz, 2C), 129.0 (4C), 129.9 (2C), 135.0 (4C), 137.4 (2C), 157.2 (d, JCeF¼13 Hz, 2C), 165.0 (d, JCeF¼247 Hz), 169.0 (2C); 19F NMR (CDCl3, 376 MHz) d 107.8; HRMS (FABþ) m/z calcd for C30H35FIN2O4 (MþH) 633.1626, found 633.1612; [a]22 D 122.2 (c 0.6, CHCl3).

400 MHz) d 18.6, 52.3, 74.1, 87.2, 113.3, 123.5, 129.3, 139.7, 156.5, 172.0. 4.2.14. (R)-2-(2-Iodophenoxy)-N-mesitylpropanamide (11b). Compound 11b was prepared as 7g from in 88% yield. Yellow solid; TLC, Rf¼0.55 (hexaneeEtOAc¼1:1); IR (KBr) 3277, 1658, 1521, 1473, 1224, 1100 cm1; 1H NMR (CDCl3, 400 MHz) d 1.77 (d, J¼6.8 Hz, 3H), 2.14 (s, 6H), 2.27 (s, 3H), 4.96 (q, J¼6.8 Hz, 1H), 6.80 (t, J¼7.6 Hz, 1H), 6.90e6.96 (m, 3H), 7.34 (t, J¼7.6 Hz, 1H), 7.82 (dd, J¼1.6, 7.6 Hz, 1H), 8.00 (br s, 1H); 13C NMR (CDCl3, 100 MHz) d 18.3 (2C), 18.7, 20.9, 75.8, 87.2, 113.1, 123.8, 129.0 (2C), 129.8, 130.0, 135.1 (2C), 137.2, 139.7, 155.1, 169.8; HRMS (FABþ) m/z calcd for C18H21INO2 (MþH) 410.0617, found 410.0609; [a]25 D þ52.1 (c 1.0, CHCl3). 4.3. Synthesis of 1-napthol derivatives 5 (Scheme 5) 4.3.1. 3-(1-Hydroxynaphthalen-2-yl)propanoic acid (5a)6,10. To a stirred solution of 1-naphtol (12a, 4.33 g, 30 mmol) and triethyl orthoacrylate (6.0 ml, 48 mmol) in toluene (100 ml) was added pivalic acid (1.53 g, 15 mmol) and the resulting mixture was refluxed for 1 day. The resulting mixture was poured into 1 M NaOH (30 mL), extracted with Et2O (twice) and washed with brine. The combined organic layers were dried over anhydrous Na2SO4 and solvents were removed in vacuo. The residue was purified by flash column chromatography on silica gel (eluent: hexaneeEtOAc¼15:1) to give 13a (8.17 g, 30 mmol, >99% yield) as colorless oil. To a solution of 13a (8.17 g, 30 mmol) in Et2O (80 ml) was added 2 M HCl (40 ml) and the resulting mixture was stirred for overnight at room temperature. The resulting mixture was extracted with EtOAc (twice) and washed with brine. The combined organic layers were dried over anhydrous Na2SO4 and solvents were removed in vacuo. To a solution of the crude product in THF (30 mL) and MeOH (30 ml) was added 2 N NaOH (40 mL) and the resulting mixture was stirred overnight at room temperature. The resulting mixture was poured into 1 N HCl (100 mL), extracted with EtOAc (twice) and washed with brine. The combined organic layers were dried over anhydrous MgSO4 and solvents were removed in vacuo. The residue was purified by flash column chromatography on silica gel (eluent: hexaneeEtOAc¼4:1 to 1:2) to give 5a (4.05 g, 18.7 mmol) in 62% yield (2 steps). White solid; TLC, Rf¼0.27 (hexaneeEtOAceCHCl3¼1:2:1 with a few drops of AcOH); 1H NMR (CDCl3, 400 MHz) d 2.86e2.89 (m, 2H), 3.02e3.06 (m, 2H), 7.17 (d, J¼8.4 Hz, 1H), 7.39 (d, J¼8.4 Hz, 1H), 7.40e7.47 (m, 2H), 7.65 (br s, 1H), 7.73e7.76 (m, 1H), 8.24e8.27 (m, 1H); 13C NMR (CDCl3, 100 MHz) d 24.1, 34.7, 120.0, 120.7, 122.1, 125.3, 125.7, 125.9, 127.3, 128.1, 133.7, 149.2, 180.5.

4.2.12. (2R,20 R)-2,20 -(2-Iodo-1,3-phenylene)bis(oxy)bis(N-mesityl-3methylbutanamide) (7l). Compound 7l was prepared as 7g in 30% yield (three steps). Yellow solid; TLC, Rf¼0.48 (hexaneeEtOAc¼ 1:1); IR (KBr) 3376, 3246, 2967, 2921, 1665, 1459, 1246, 1079 cm1; 1 H NMR (CDCl3, 400 MHz) d 1.19 (d, J¼7.2 Hz, 6H), 1.31 (d, J¼7.2 Hz, 6H), 2.05 (s, 12H), 2.24 (s, 6H), 2.45e2.52 (m, 2H), 4.73 (q, J¼6.8 Hz, 2H), 6.62 (d, J¼8.4 Hz, 2H), 6.86 (s, 4H), 7.28 (t, J¼8.4 Hz, 1H), 7.60 (s, 2H); 13C NMR (CDCl3, 100 MHz) d 17.6 (2C), 18.5 (4C), 19.1 (2C), 20.8 (2C), 31.7 (2C), 79.3, 84.4 (2C), 106.5 (2C), 129.0 (4C), 130.0 (2C), 130.6, 134.8 (4C), 137.1 (2C), 157.6 (2C), 168.4 (2C); HRMS (FABþ) m/z calcd for C34H44IN2O4 (MþH) 671.2346, found 671.2342; [a]26 D 63.7 (c 1.0, CHCl3).

4.3.2. 3-(1-Hydroxy-4-methylnaphthalen-2-yl)propanoic acid (5b). This compound was prepared as 5a from 4-methylnaphthalen-1ol (12b) in 62% yield (three steps). White solid; TLC, Rf¼0.50 (hexaneeEtOAceCHCl3¼1:2:1 with a few drops of AcOH); IR (film) 3500e3200, 3010, 1765, 1703, 1387, 1147 cm1; 1H NMR (CDCl3, 400 MHz) d 2.57 (s, 3H), 2.85 (t, J¼6.9 Hz, 2H), 2.99 (t, J¼6.9 Hz, 2H), 6.99 (s, 1H), 7.44e7.49 (m, 2H), 7.84e7.88 (m, 1H), 8.24e8.28 (m, 1H); 13C NMR (CDCl3, 100 MHz) d 18.7, 24.0, 34.7, 119.5, 122.7, 123.8, 125.0, 125.7, 126.0, 126.6, 128.4, 132.5, 147.7, 180.3; HRMS (FABþ) m/z calcd for C14H15O3 (MþH) 231.1021, found 231.1025.

4.2.13. (R)-Methyl 2-(2-iodophenoxy)propanoate (11a)3g. Compound 11a was prepared as 7a from 2-iodophenol with ()-lactic acid methylester in 80% yield. Pale yellow oil; TLC, Rf¼0.40 (hexaneeEtOAc¼4:1); 1H NMR (CDCl3, 400 MHz) d 1.69 (d, J¼6.9 Hz, 3H), 3.75 (s, 3H), 4.88 (q, J¼6.9 Hz, 1H), 6.64e6.77 (m, 2H), 7.24 (t, J¼7.8 Hz, 1H), 7.77 (dd, J¼1.8, 7.8 Hz, 1H); 13C NMR (CDCl3,

4.3.3. 3-(4-Chloro-1-hydroxynaphthalen-2-yl)propanoic acid (5c). This compound was prepared as 5a from 4-chloronaphthalen-1-ol (12c) in 40% yield (three steps). White solid; TLC, Rf¼0.50 (hexaneeEtOAceCHCl3¼1:2:1 with a few drops of AcOH); IR (KBr) 3500e3200, 1691, 1595, 1449, 1381, 1259 cm1; 1H NMR (DMSO-d6, 400 MHz) d 2.57 (t, J¼7.8 Hz, 2H), 2.98 (t, J¼7.8 Hz, 2H), 7.48 (s, 1H),

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7.54e7.63 (m, 2H), 8.03 (d, J¼7.3 Hz, 1H), 8.27 (d, J¼7.3 Hz, 1H), 9.48 (br s, 1H), 12.18 (br s, 1H); 13C NMR (DMSO-d6, 100 MHz) d 25.0, 34.0, 120.5, 122.5, 122.7, 123.5, 125.8, 126.5, 126.8, 128.5, 129.4, 149.1, 174.1; HRMS (FABþ) m/z calcd for C13H12ClO3 (MþH) 251.0475, found 251.0479. 4.3.4. 3-(4-Bromo-1-hydroxynaphthalen-2-yl)propanoic acid (5d)6. This compound was prepared as 5a from 4-bromonaphthalen-1-ol (12d) in 71% yield (3 steps). Yellow solid; TLC, Rf¼0.50 (hexaneeEtOAceCHCl3¼1:2:1 with a few drops of AcOH); IR (KBr) 3500e3200, 1692, 1595, 1449, 1378, 1241 cm1; 1H NMR (CDCl3, 400 MHz) d 2.87e2.90 (m, 2H), 3.00e3.03 (m, 2H), 7.48 (s, 1H), 7.51 (dt, J¼1.2, 7.2 Hz, 1H), 7.56 (dt, J¼1.2, 7.2 Hz, 1H), 7.50e7.70 (br s, 1H), 8.08 (d, J¼7.2 Hz, 1H), 8.25 (d, J¼7.2 Hz, 1H); 13C NMR (CDCl3, 100 MHz) d 23.8, 34.6, 113.4, 121.0, 122.8, 126.1, 126.7, 127.1, 127.3, 131.4, 131.7, 149.4, 180.3; HRMS (FABþ) m/z calcd for C13H11BrO3 (M) 293.9892, found 293.9896. 4.3.5. 3-(1-Hydroxy-4-phenylnaphthalen-2-yl)propanoic acid (5e). This compound was prepared as 5a from 4-phenylnaphthalen-1ol (12e) in 73% yield (three steps). Pale yellow solid; TLC, Rf¼0.50 (hexaneeEtOAceCHCl3¼1:2:1 with a few drops of AcOH); IR (KBr) 3500e3200, 1699, 1578, 1391, 1304, 1220 cm1; 1H NMR (DMSO-d6, 500 MHz) d 2.59 (t, J¼7.5 Hz, 2H), 3.03 (t, J¼7.5 Hz, 2H), 7.23 (s, 1H), 7.39e7.51 (m, 7H), 7.73 (d, J¼7.5 Hz, 2H), 8.28 (d, J¼7.5 Hz, 1H), 9.25 (br s, 1H), 12.05 (br s, 1H); 13C NMR (DMSO-d6, 100 MHz) d 25.3, 34.3, 121.3, 122.4, 124.8, 125.0, 125.5, 125.6, 126.9, 128.4 (2C), 129.6, 129.9 (2C), 130.6, 131.0, 140.4, 149.2, 174.4; HRMS (FABþ) m/z calcd for C19H17O3 (MþH) 293.1178, found 293.1174. 4.3.6. 3-(4-Benzoyl-1-hydroxynaphthalen-2-yl)propanoic acid (5f)6. This compound was prepared as 5a from (4-hydroxynaphthalen1-yl)(phenyl)methanone (12f) in 77% yield (three steps). White solid; TLC, Rf¼0.50 (hexaneeEtOAceCHCl3¼1:2:1 with a few drops of AcOH); IR (KBr) 3500e3200, 1685, 1562, 1503, 1269, 1242 cm1; 1H NMR (DMSO-d6, 400 MHz) d 2.55 (t, J¼7.3 Hz, 2H), 2.99 (t, J¼7.3 Hz, 2H), 7.40e7.57 (m, 5H), 7.67 (t, J¼7.3 Hz, 1H), 7.74 (d, J¼8.3 Hz, 2H), 8.21 (d, J¼8.3 Hz, 1H), 8.34 (d, J¼7.8 Hz, 1H), 10.10 (br s, 1H), 12.10 (br s, 1H); 13C NMR (DMSO-d6, 100 MHz) d 25.2, 33.9, 119.8, 122.4, 125.2, 125.3, 125.5, 126.1, 127.0, 128.6 (2C), 129.9 (2C), 131.2, 132.7, 133.8, 138.9, 153.4, 174.0, 196.2; HRMS (FABþ) m/z calcd for C20H17O4 (MþH) 321.1127, found 321.1133. 4.3.7. 3-(4-(4-Bromobenzoyl)-1-hydroxynaphthalen-2-yl)propanoic acid (5g). This compound was prepared as 5a from (4-bromophenyl)(4-hydroxynaphthalen-1-yl)methanone (12g) in 70% yield (three steps). Pale yellow solid; TLC, Rf¼0.50 (hexaneeEtOAceCHCl3¼1:2:1 with a few drops of AcOH); IR (KBr) 3500e3200, 1716, 1699, 1628, 1570, 1509, 1260 cm1; 1H NMR (DMSO-d6, 400 MHz) d 2.55 (t, J¼7.3 Hz, 2H), 2.99 (t, J¼7.3 Hz, 2H), 7.52 (s, 1H), 7.52e7.57 (m, 2H), 7.66 (d, J¼8.2 Hz, 2H), 7.74 (d, J¼8.7 Hz, 2H), 8.23e8.27 (m, 1H), 8.33e8.36 (m, 1H), 10.18 (br s, 1H), 12.16 (br s, 1H); 13C NMR (DMSO-d6, 125 MHz) d 25.1, 33.9, 119.8, 122.4, 125.2, 125.3 (2C), 125.5, 126.7, 127.2, 131.2, 131.6 (2C), 131.9 (2C), 134.3, 137.9, 153.7, 174.0, 196.1; HRMS (FABþ) m/z calcd for C20H15BrO4 (M) 398.0154, found 398.0155. 4.3.8. 3-(1-Hydroxy-4-methoxynaphthalen-2-yl)propanoic acid (5h)6. This compound was prepared as 5a from 4-methoxynaphthalen-1-ol (12h) in 54% yield (three steps). White solid; TLC, Rf¼0.50 (hexaneeEtOAceCHCl3¼1:2:1 with a few drops of AcOH); 1H NMR (CDCl3, 400 MHz) d 2.89 (t, J¼6.4 Hz, 2H), 3.04 (t, J¼6.4 Hz, 2H), 3.95 (s, 3H), 6.49 (s, 1H) 7.18e7.28 (br s, 1H), 7.45 (t, J¼8.4 Hz, 1H), 7.50 (t, J¼8.4 Hz, 1H), 8.14 (d, J¼8.4 Hz, 1H), 8.21

5847

(d, J¼8.4 Hz, 1H); 13C NMR (CDCl3, 100 MHz) d 24.5, 34.7, 55.7, 105.5, 119.6, 121.6, 122.0, 125.3, 125.4, 126.0, 126.7, 142.7, 149.7, 180.3. 4.3.9. 3-(1-Hydroxy-6-methoxynaphthalen-2-yl)propanoic acid (5i). This compound was prepared as 5a from 6-methoxynaphthalen-1-ol (12i) in 60% yield (three steps). Yellow solid; TLC, Rf¼0.50 (hexaneeEtOAceCHCl3¼1:2:1 with a few drops of AcOH); IR (KBr) 3542, 3484, 1686, 1418, 1360, 1229, 1163 cm1; 1H NMR (DMSO-d6, 400 MHz) d 2.50e2.53 (m, 2H), 2.91 (t, J¼7.3 Hz, 2H), 3.84 (s, 3H), 7.07 (dd, J¼2.8, 9.2 Hz, 1H) 7.17e7.26 (m, 3H), 8.08 (d, J¼9.0 Hz, 1H), 9.07 (br s, 1H), 12.10 (br s, 1H); 13C NMR (DMSO-d6, 100 MHz) d 25.2, 34.4, 55.1, 105.7, 117.0, 118.2, 119.5, 120.6, 123.6, 129.1, 134.6, 149.7, 156.8, 174.4; HRMS (FABþ) m/z calcd for C14H15O4 (MþH) 247.0970, found 247.0965. 4.3.10. 3-(1-Hydroxy-3-methoxynaphthalen-2-yl)propanoic acid (5j). This compound was prepared as 5a from 3-methoxynaphthalen-1-ol (12j) in 40% yield (three steps). Pale brown solid; TLC, Rf¼0.46 (hexaneeEtOAceCHCl3¼1:2:1 with a few drops of AcOH); IR (KBr) 3394, 3406, 2943, 1697, 1446, 1406, 1268, 1116 cm1; 1H NMR (DMSO-d6, 400 MHz) d 2.42 (t, J¼8.0 Hz, 2H), 2.98 (t, J¼8.0 Hz, 2H), 3.87 (s, 3H), 6.87 (s, 1H), 7.27 (t, J¼7.3 Hz, 1H), 7.37 (t, J¼7.3 Hz, 1H), 7.69 (d, J¼7.8 Hz, 1H), 8.08 (d, J¼8.2 Hz, 1H), 9.20 (br s, 1H), 12.19 (br s, 1H); 13C NMR (DMSO-d6, 100 MHz) d 19.1, 33.5, 55.5, 97.8, 113.9, 121.2, 121.9, 122.4, 125.9, 126.4, 133.2, 150.4, 156.5, 174.8; HRMS (FABþ) m/z calcd for C14H15O4 (MþH) 247.0970, found 247.0971. 4.3.11. 3-(3-(Benzyloxymethyl)-1-hydroxynaphthalen-2-yl)propanoic acid (5k). This compound was prepared as 5a from 3benzyloxymethylnaphthalen-1-ol (12k) in 53% yield (three steps). Pale yellow solid; TLC, Rf¼0.38 (hexaneeEtOAce CHCl3¼1:2:1 with a few drops of AcOH); IR (KBr) 3233, 2874, 1696, 1362, 1250, 1033 cm1; 1H NMR (CDCl3, 400 MHz) d 2.84 (t, J¼5.0 Hz, 1H), 3.11 (t, J¼5.0 Hz, 1H), 4.56 (s, 2H), 4.65 (s, 2H), 7.24e7.46 (m, 8H), 7.71e7.73 (m, 1H), 8.22e8.23 (m, 1H); 13C NMR (CDCl3, 100 MHz) d 20.0, 34.2, 71.5, 72.0, 119.9, 122.0, 122.4, 125.5, 125.7, 126.2, 127.3, 127.8, 128.1 (2C), 128.5 (2C), 132.9, 134.2, 137.7, 150.4, 180.8; HRMS (FABþ) m/z calcd for C21H21O4 (MþH) 337.1440, found 337.1434. 4.4. Preparation of iodosylarene 14 (Scheme 6)6 A solution of 7g (61.5 mg, 0.1 mmol) and SelectfluorÒ (177 mg, 0.5 mmol) in AcOH (1 mL) and CH3CN (3.2 mL) was stirred for 5 h at room temperature. After CH3CN was evaporated in vacuo, water was added to the residue and the resulting solution was extracted with CH2Cl2 (twice), and washed with water. The combined organic layers were dried over anhydrous Na2SO4. The solvents were removed in vacuo to give 14 (66 mg, 0.09 mmol, contained ca. 10% of 7g) in 90% yield. White powder; IR (film) 3317, 3008, 1677, 1517, 1464, 1252, 1094 cm1; The 1H and 13C NMR spectra of 14 were assigned by using a combination of 2D NMR experiments, which included HMQC and HMBC studies: 1H NMR (CDCl3, 400 MHz, Ar1¼Iodoarene, Ar2¼Mesitylene) d 1.50 (s, 6H, IOCOCH3), 1.80e1.90 (br s, 12H, 2-CH3eAr2), 1.88 (d, J¼6.5 Hz, 6H, eOCH(CH3)COe), 2.21 (s, 6H, 4-CH3eAr2), 5.15 (q, J¼6.5 Hz, 2H, eOCH(CH3)COe), 6.79 (s, 4H, 3HeAr2), 6.94 (d, J¼8.5 Hz, 2H, 3HeAr1), 7.57 (t, J¼8.5 Hz, 1H, 4HeAr1), 8.34 (s, 2H, NH); 13C NMR (CDCl3, 100 MHz) d 17.6 (4C), 19.4 (2C), 19.5 (2C), 20.9 (4C), 76.2 (2C), 103.5, 106.3 (2C), 129.0 (4C), 129.6 (4C), 134.9 (2C), 136.5, 137.4 (2C), 156.0 (2C), 169.6 (2C), 176.7 (2C); HRMS (FABþ) m/z calcd for C32H38IN2O6 (MeOAc) 673.1775, found 673.1779.

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4.5. Representative procedure for 8g-catalyzed enantioselective oxidative dearomatization of 5 with mCPBA (Tables 1e3) 4.5.1. (þ)-10 H,3H-Spiro[furan-2,20 -naphthalene]-10,5(4H)-dione (6a, Table 2, entry 3)6. A solution of 5a (216 mg, 1.0 mmol), 7g (92.2 mg, 0.15 mmol, 15 mol %), and mCPBA (269 mg, 1.2 mmol, 1.2 equiv) in CHCl3 (50 mL) was stirred at 0  C. After 18 h, the resulting mixture poured into aqueous Na2S2O3 (20 mL) and aqueous NaHCO3, and extracted with CHCl3 (two times). The organic layers were dried over anhydrous MgSO4 and solvents were removed in vacuo. The residue was purified by flash column chromatography on silica gel (eluent: hexaneeEtOAc¼10:1 to 4:1) to give 6a (129 mg, 0.6 mmol) in 60% yield. White solid; TLC, Rf¼0.46 (hexaneeEtOAceCHCl3¼1:2:1); 1H NMR (CDCl3, 400 MHz) d 2.18 (ddd, J¼9.6, 11.0, 13.5 Hz, 1H), 2.49 (ddd, J¼1.8, 9.6, 13.5 Hz, 1H), 2.60 (ddd, J¼1.8, 9.6, 17.6 Hz, 1H), 2.92 (ddd, J¼9.6, 11.0, 17.6 Hz, 1H), 6.21 (d, J¼10.4 Hz, 1H), 6.66 (d, J¼10.4 Hz, 1H), 7.26 (d, J¼8.0 Hz, 1H), 7.41 (t, J¼8.0 Hz, 1H), 7.62 (t, J¼8.0 Hz, 1H), 8.02 (d, J¼8.0 Hz, 1H); 13 C NMR (CDCl3, 100 MHz) d 26.5, 31.2, 83.4, 127.3, 127.8, 127.9, 127.9, 129.0, 132.3, 135.7, 136.8, 176.5, 196.5; HPLC (OD-H column), hexaneeiPrOH¼85:15 as eluent, 1.0 mL/min, tR¼19.4 min (major), 25.1 min (minor); [a]26 D þ181.7 (c 1.2, CHCl3) for 92% ee. 4.6. Representative procedure for the stoichiometric oxidation of 5 with 14 (Scheme 6 and Table 4) A solution of 5a (10.8 mg, 0.05 mmol) and 14 (36.6 mg, 0.05 mmol) in CHCl3 (2.5 mL) was stirred at 20  C. After 19 h, the resulting mixture poured into aqueous Na2S2O3 (5 mL) and aqueous NaHCO3, and extracted with CHCl3 (two times). The organic layers were dried over anhydrous MgSO4 and solvents were removed in vacuo. The residue was purified by flash column chromatography on silica gel (eluent: hexaneeEtOAc¼10:1 to 4:1) to give 6a (7.5 mg, 0.035 mmol) in 70% yield and 90% ee. 4.6.1. (þ)-40 -Methyl-10 H,3H-spiro[furan-2,20 -naphthalene]-10,5(4H)dione (6b; Table 3, entry 1 and Table 4, entry 2). Colorless amorphous; TLC, Rf¼0.40 (hexaneeEtOAc¼1:1); IR (film) 3027, 1783, 1696, 1599, 1453, 1175 cm1; 1H NMR (CDCl3, 400 MHz) d 2.12e2.24 (m, 1H), 2.21 (s, 3H), 2.41 (ddd, J¼1.8, 9.6, 13.3 Hz, 1H), 2.59 (ddd, J¼1.8, 9.6, 17.6 Hz, 1H), 2.91 (ddd, J¼9.6, 11.4, 17.6 Hz, 1H), 6.03 (s, 1H), 7.40e7.46 (m, 2H), 7.69 (dt, J¼1.4, 7.8 Hz, 1H), 8.05 (dd, J¼1.4, 7.8 Hz, 1H); 13C NMR (CDCl3, 125 MHz) d 19.3, 26.8, 31.5, 83.5, 124.8, 127.3, 127.9, 128.7, 129.0, 133.1, 135.6, 137.9, 176.5, 196.8; HRMS (FABþ) m/z calcd for C14H13O3 (MþH) 229.0865, found 229.0862; HPLC (AD-3 column), hexaneeiPrOH¼85:15 as eluent, 0.7 mL/min, tR¼20.8 min (minor), 25.3 min (major); [a]26 D þ102.4 (c 0.61, CHCl3) for 84% ee. 4.6.2. (þ)-40 -Chlorospiro[tetrahydrofuran-2,20 -(10 H-naphthaline)]10,5-dione (6c; Table 3, entry 2). White solid; TLC, Rf¼0.43 (hexaneeEtOAc¼1:1); IR (film) 3018, 1788, 1700, 1595, 1454, 1293 cm1; 1H NMR (CDCl3, 400 MHz) d 2.23 (ddd, J¼9.6, 11.0, 13.4 Hz, 1H), 2.45 (ddd, J¼2.3, 9.6, 13.4 Hz, 1H), 2.62 (ddd, J¼2.3, 9.6, 17.9 Hz, 1H), 2.91 (ddd, J¼9.6, 11.0, 17.9 Hz, 1H), 6.40 (s, 1H), 7.52 (dt, J¼1.8, 7.4 Hz, 1H), 7.70e7.79 (m, 2H), 8.06 (d, J¼7.4 Hz, 1H); 13C NMR (CDCl3, 100 MHz) d 26.5, 31.5, 83.4, 126.1, 127.3, 128.1, 129.1, 130.1, 131.8, 134.5, 135.8, 175.7, 194.7; HRMS (FABþ) m/z calcd for C13H10ClO3 (MþH) 249.0318, found 249.0316; HPLC (OD-H column), hexaneeiPrOH¼85:15 as eluent, 1.0 mL/min, tR¼18.4 min (major), 22.2 min (minor); [a]24 D þ99.0 (c 0.89, CHCl3) for 90% ee. 4.6.3. (þ)-40 -Bromospiro[tetrahydrofuran-2,20 -(10 H-naphthaline)]10,5-dione (6d; Table 3, entry 3)6. Recrystallization of 6d (85% ee) was carried out in the solution of CH3CN at room temperature to

give colorless crystal (low ee). The enantioselectivities of the mother liquid was 98% ee. White solid; TLC, Rf¼0.43 (hexaneeEtOAc¼1:1); IR (film) 3029, 1791, 1699, 1592, 1453, 1187 cm1; 1H NMR (CDCl3, 400 MHz) d 2.24 (ddd, J¼9.6, 11.0, 13.5 Hz, 1H), 2.46 (ddd, J¼2.3, 9.6, 13.5 Hz, 1H), 2.62 (ddd, J¼2.3, 9.6, 17.9 Hz, 1H), 2.90 (ddd, J¼9.6, 11.0, 17.9 Hz, 1H), 6.67 (s, 1H), 7.49e7.53 (m, 1H), 7.73e7.78 (m, 2H), 8.05 (d, J¼7.2 Hz, 1H); 13C NMR (CDCl3, 100 MHz) d 26.5, 31.2, 84.2, 122.5, 127.0, 128.0, 128.8, 130.1, 133.4, 135.1, 135.9, 175.7, 194.7; HRMS (FABþ) m/z calcd for C13H10BrO3 (MþH) 292.9813, found 292.9814; HPLC (OD-H column), hexaneeiPrOH¼85:15 as eluent, 1.0 mL/min, tR¼18.8 min (major), 22.3 min (minor); [a]26 D þ91.8 (c 1.6, CHCl3) for 98% ee. 4.6.4. (þ)-40 -Phenyl-10 H,3H-spiro[furan-2,20 -naphthalene]-10,5 (4H)dione (6e; Table 3, entry 4). Recrystallization of 6e (87% ee) was carried out in the solution of iPrOH at room temperature to give colorless crystal (98% ee). TLC, Rf¼0.47 (hexaneeEtOAc¼1:1); IR (film) 3027, 1783, 1687, 1593, 1280, 1176 cm1; 1H NMR (CDCl3, 400 MHz) d 2.27 (ddd, J¼9.6, 11.0, 13.3 Hz, 1H), 2.54 (ddd, J¼2.3, 9.6, 13.3 Hz, 1H), 2.63 (ddd, J¼2.3, 9.6, 17.6 Hz, 1H), 2.93 (ddd, J¼9.6, 11.0, 17.6 Hz, 1H), 6.12 (s, 1H), 7.15 (d, J¼7.3 Hz, 1H), 7.34e7.50 (m, 6H), 7.56 (dt, J¼1.4, 7.3 Hz, 1H), 8.10 (dd, J¼1.4, 7.3 Hz, 1H); 13C NMR (CDCl3, 100 MHz) d 26.7, 31.5, 83.7, 127.4, 127.6, 128.2, 128.4, 128.6 (2C), 128.7 (2C), 128.9, 130.6, 135.3, 137.4, 137.6, 139.8, 176.3, 196.4; HRMS (FABþ) m/z calcd for C19H15O3 (MþH) 291.1021, found 291.1021; HPLC (OD-H column), hexaneeiPrOH¼85:15 as eluent, 1.0 mL/min, tR¼20.0 min (minor), 31.2 min (major); [a]26 D þ115.9 (c 0.19, CHCl3) for 98% ee. 4.6.5. ()-(R)-40 -Benzoyl-10 H,3H-spiro[furan-2,20 -naphthalene]-10,5 (4H)-dione (6f; Table 3, entry 5)6. Colorless crystal; TLC, Rf¼0.40 (hexaneeEtOAc¼1:1); IR (KBr) 3069, 2944, 1783, 1692, 1591, 1455, 1190 cm1; 1H NMR (CDCl3, 400 MHz) d 2.27 (ddd, J¼9.6, 11.0, 13.3 Hz, 1H), 2.52 (ddd, J¼1.8, 9.6, 13.3 Hz, 1H), 2.63 (ddd, J¼1.8, 9.6, 17.6 Hz, 1H), 2.92 (ddd, J¼9.6, 11.0, 17.6 Hz, 1H), 6.39 (s, 1H), 7.41 (d, J¼7.8 Hz, 1H), 7.46e7.52 (m, 3H), 7.60e7.67 (m, 2H), 7.96 (d, J¼7.3 Hz, 2H), 8.12 (dd, J¼1.4, 7.8 Hz, 1H); 13C NMR (CDCl3, 100 MHz) d 26.3, 31.2, 82.7, 126.9, 127.4, 128.5, 128.9 (2C), 129.8, 130.1 (2C), 134.0, 134.2, 134.3, 135.8, 136.0, 1375, 175.8, 194.5, 195.2; HRMS (FABþ) m/z calcd for C20H15O4 (MþH) 319.0970, found 319.0971; HPLC (OD-H column), hexaneeiPrOH¼85:15 as eluent, 1.0 mL/min, tR¼32.4 min (major, R), 40.2 min (minor, S); [a]26 D 35.2 (c 0.41, CHCl3) for >99% ee. 4.6.6. X-ray crystallographic analysis of ()-6f (Fig. 2). Recrystallization of ()-6f (83% ee) was carried out in the solution of iPrOH at room temperature to give colorless crystal (>99% ee). Mp: 153e155  C. Crystal data: formula C20H14O4, M¼318.31, colorless, crystal dimensions 0.500.400.20 mm3, orthorhombic, A, b¼10.164(3)  A, c¼28.448 space group P212121, a¼5.4071(16)  (8)  A, V¼1563.4(8)  A3, Z¼4, Dcalcd¼1.352 g/cm3, F(000)¼664, m (Mo Ka)¼0.094 mm1, T¼173(2) K. X-ray crystallographic analysis was performed with a Bruker SMART APEX diffractometer A) and (graphite monochromator, Mo Ka radiation, l¼0.71073  the structure was solved by direct methods and expanded using Fourier techniques (Sir97 and SHELXL17). 11,371 reflections collected, 3876 independent reflections with I>2s(I) (2qmax¼28.33 ), and 265 parameters were used for the solution of the structure. The non-hydrogen atoms were refined anisotropically. R1¼0.0411 and wR2¼0.0848, GOF¼1.017. Crystallographic data (excluding structure factors) for the structure reported in this paper have been deposited with the Cambridge Crystallographic Data Center as supplementary publication no. CCDC-758468 for ()-6f. Copies of the data can be obtained free of charge on application to CCDC, 12 Union Road, Cambridge CB2

M. Uyanik et al. / Tetrahedron 66 (2010) 5841e5851

1EZ, UK [fax: int. code þ44 1223 336 033; e-mail: deposit@ccdc. cam.ac.uk]. 4.6.7. ()-40 -(4-Bromobenzoyl)-10 H,3H-spiro[furan-2,20 -naphthalene]-10,5(4H)-dione (6g; Table 3, entry 6). White solid; TLC, Rf¼0.43 (hexaneeEtOAc¼1:1); IR (film) 3027, 1793, 1698, 1669, 1585, 1278, 1172 cm1; 1H NMR (CDCl3, 400 MHz) d 2.27 (ddd, J¼9.6, 11.0, 13.3 Hz, 1H), 2.52 (ddd, J¼1.8, 9.6, 13.3 Hz, 1H), 2.63 (ddd, J¼1.8, 9.6, 17.6 Hz, 1H), 2.92 (ddd, J¼9.6, 11.0, 17.6 Hz, 1H), 6.38 (s, 1H), 7.37 (d, J¼7.8 Hz, 1H), 7.50 (dt, J¼0.9, 7.8 Hz, 1H), 7.60e7.66 (m, 3H), 7.83 (d, J¼8.7 Hz, 2H), 8.12 (dd, J¼1.4, 7.8 Hz, 1H); 13C NMR (CDCl3, 100 MHz) d 26.2, 31.2, 82.5, 126.8, 127.3, 128.6, 129.8, 129.9, 131.4 (2C), 132.3 (2C), 133.7, 134.2, 134.7, 135.8, 137.2, 175.7, 193.5, 195.0; HRMS (FABþ) m/z calcd for C20H14BrO4 (MþH) 397.0075, found 397.0079; HPLC (OD-H column), hexaneeiPrOH¼85:15 as eluent, 1.0 mL/min, tR¼44.3 min (major), 49.7 min (minor); [a]24 D 44.0 (c 1.83, CHCl3) for 84% ee. 4.6.8. 40 -Methoxyspiro[tetrahydrofuran-2,20 -(10 H-naphthaline)]-10,5dione (6h; Table 3, entry 7)6. White solid; TLC, Rf¼0.33 (hexaneeEtOAc¼1:1); 1H NMR (CDCl3, 400 MHz) d 2.17 (ddd, J¼9.6, 11.0, 13.6 Hz, 1H), 2.49 (ddd, J¼2.3, 9.6, 13.6 Hz, 1H), 2.61 (ddd, J¼2.3, 9.6, 17.6 Hz, 1H), 2.95 (ddd, J¼9.6, 11.0, 17.6 Hz, 1H), 3.84 (s, 3H), 5.17 (s, 1H), 7.46 (t, J¼7.6 Hz, 1H), 7.67 (t, J¼7.6 Hz, 1H), 7.74 (d, J¼7.6 Hz, 1H), 8.00 (d, J¼7.6 Hz, 1H); 13C NMR (CDCl3, 100 MHz) d 27.6, 33.0, 55.1, 83.8, 99.9, 123.1, 127.2, 127.5, 129.4, 134.6, 135.3, 152.0, 176.6, 195.7. 4.6.9. (þ)-6 0 -Methoxy-1 0 H,3H-spiro[furan-2,2 0 -naphthalene]-1 0,5 (4H)-dione (6i; Table 3, entry 8 and Table 4, entry 3). White solid; TLC, Rf¼0.27 (hexaneeEtOAc¼1:1); IR (KBr) 3027, 1787, 1683, 1597, 1273, 1176 cm1; 1H NMR (CDCl3, 400 MHz) d 2.17 (ddd, J¼9.6, 11.0, 13.3 Hz, 1H), 2.40 (ddd, J¼2.2, 9.6, 13.3 Hz, 1H), 2.61 (ddd, J¼2.2, 9.6, 17.6 Hz, 1H), 2.95 (ddd, J¼9.6, 11.0, 17.6 Hz, 1H), 3.94 (s, 3H), 6.21 (d, J¼9.6 Hz, 1H), 6.60 (d, J¼9.6 Hz, 1H), 6.72 (d, J¼2.8 Hz, 1H), 6.91 (dd, J¼2.8, 8.7 Hz, 1H), 8.01 (d, J¼8.7 Hz, 1H); 13C NMR (CDCl3, 100 MHz) d 26.8, 31.6, 55.7, 82.8, 112.9, 114.2, 120.6, 127.9, 130.5, 133.3, 139.1, 165.6, 176.3, 194.8; HRMS (FABþ) m/z calcd for C14H13O4 (MþH) 245.0814, found 245.0810; HPLC (AD-3 column), hexaneeiPrOH¼85:15 as eluent, 0.7 mL/min, tR¼33.8 min (minor), 39.6 min (major); [a]25 D þ146.8 (c 0.06, CHCl3) for 87% ee. 4.6.10. (þ)-30 -Methoxy-10 H,3H-spiro[furan-2,20 -naphthalene]-10,5 (4H)-dione (6j; Table 3, entry 9 and Table 4, entry 4). Pale yellow solid; TLC, Rf¼0.50 (hexaneeEtOAc¼1:1); IR (KBr) 3027, 1792, 1691, 1650, 1191, 1168 cm1; 1H NMR (CDCl3, 400 MHz) d 2.34e2.48 (m, 2H), 2.70 (ddd, J¼5.0, 9.6, 17.6 Hz, 1H), 2.87 (ddd, J¼8.2, 10.6, 17.6 Hz, 1H), 3.82 (s, 3H), 5.73 (s, 1H), 7.15 (d, J¼7.3 Hz, 1H), 7.23 (dt, J¼0.9, 7.3 Hz, 1H), 7.54 (dt, J¼1.4, 7.3 Hz, 1H), 7.95 (d, J¼7.3 Hz, 1H); 13 C NMR (CDCl3, 100 MHz) d 27.4, 30.5, 55.8, 82.8, 98.3, 124.7, 126.4, 126.8, 128.1, 136.0, 138.2, 157.6, 176.6, 195.2; HRMS (FABþ) m/z calcd for C14H13O4 (MþH) 245.0814, found 245.0814; HPLC (AD-3 column), hexaneeiPrOH¼85:15 as eluent, 0.7 mL/min, tR¼28.2 min (minor), 29.9 min (major); [a]26 D þ98.2 (c 0.53, CHCl3) for 95% ee. 4.6.11. (þ)-30 -(Benzyloxymethyl)-10 H,3H-spiro[furan-2,20 -naphthalene]-10,5(4H)-dione (6k; Table 3, entry 10 and Table 4, entry 5). Colorless amorphous; TLC, Rf¼0.43 (hexaneeEtOAc¼1:1); IR (film) 1784, 1697, 1600, 1455, 1290, 1180, 1097 cm1; 1H NMR (CDCl3, 400 MHz) d 2.30e2.37 (m, 1H), 2.43e2.55 (m, 2H), 2.69e2.79 (m, 1H), 4.25 (d, J¼12.8 Hz, 1H), 4.36 (d, J¼12.8 Hz, 1H), 4.60 (s, 2H), 6.70 (s, 1H), 7.25 (d, J¼7.8 Hz, 1H) 7.30e7.40 (m, 6H), 7.62 (t, J¼7.8 Hz, 1H), 7.98 (d, J¼7.8 Hz, 1H); 13C NMR (CDCl3, 100 MHz) d 26.1, 30.4, 68.9, 73.3, 85.8, 124.6, 126.7, 127.7, 127.8 (2C), 128.0 (2C), 128.5 (2C), 128.6 135.6, 136.8, 137.5, 140.0, 176.6, 196.9; HRMS (FABþ) m/z calcd for C21H19O4 (MþH) 335.1283, found 335.1292;

5849

HPLC (OD-H column), hexaneeiPrOH¼85:15 as eluent, 1.0 mL/min, tR¼27.4 min (minor), 69.0 min (major); [a]23 D þ156.2 (c 0.5, CHCl3) for 94% ee. 4.7. One-pot oxidation of 5a to epoxyspirolactone (L)-15 (Scheme 7) 4.7.1. ()-(1a0 R,2R,7b0 R)-1a0 H,3H-Spiro[furan-2,20 -naphtho[1,2-b] oxirene]-30 ,5(4H,7b0 H)-dione (15). A solution of 5a (10.8 mg, 0.05 mmol), 7g (4.6 mg, 0.0075 mmol, 10 mol %), and mCPBA (43.1 mg, 0.25 mmol, 1.3 equiv) in CHCl3 (1.7 mL) and CH3NO2 (1.7 mL) mixed solvents was stirred at 0  C for 24 h and at room temperature for 72 h. The solvents were removed in vacuo. The conversion of 5a to epoxyspirolactones 15 and 16 (84% conv.) and the diastereomeric ratio (15e16¼64:36) were determined by 1H NMR analysis of the crude mixture. The residue was purified by flash column chromatography on silica gel (eluent: hexaneeEtOAc¼10:1 to 2:1) to give ()-15 (6.0 mg, 0.026 mmol) as a single compound in 52% yield. Recrystallization of ()-15 (88% ee) was carried out in the solution of EtOH at room temperature to give colorless thin needles (>99% ee). TLC, Rf¼0.13 (hexanee EtOAc¼1:1); IR (film) 1793, 1706, 1210, 1181 cm1; 1H NMR (CDCl3, 400 MHz) d 2.04e2.11 (m, 1H), 2.27e2.36 (m, 1H), 2.57e2.73 (m, 2H), 3.92 (d, J¼4.2 Hz, 1H), 4.18 (d, J¼4.2 Hz, 1H), 7.53e7.57 (m, 1H), 7.64e7.69 (m, 2H), 8.00 (d, J¼7.8 Hz, 1H); 13C NMR (CDCl3, 100 MHz) d 26.5, 28.7, 52.4, 55.9, 85.2, 129.0, 129.7, 130.0 (2C), 134.5, 137.8, 175.7, 191.6; HRMS (FABþ) m/z calcd for C13H11O4 (MþH) 231.0657, found 231.0657; HPLC (OD-H column), hexaneeEtOH¼4:1 as eluent, 1.0 mL/min, tR¼19.8 min (major), 26.2 min (minor); [a]24 D 73.8 (c 1.6, CHCl3) for 92% ee. 4.7.2. X-ray crystallographic analysis of ()-15 (Fig. 3). Recrystallization of ()-15 was carried out in the solution of EtOH at room temperature to give colorless crystal. Mp: 199e201  C. Crystal data: formula C13H10O4, M¼230.21, colorless, crystal dimensions 0.200.100.10 mm3, orthorhombic, space group Pbca, a¼8.8107 (19)  A, b¼11.238(2)  A, c¼21.064(4)  A, V¼2085.6(8)  A3, Z¼8, Dcalcd¼1.466 g/cm3, F(000)¼960, m(Mo Ka)¼0.110 mm1, T¼143(2) K. X-ray crystallographic analysis was performed with a Bruker SMART APEX diffractometer (graphite monochromator, Mo Ka raA) and the structure was solved by direct diation, l¼0.71073  methods and expanded using Fourier techniques (Sir97 and SHELXL17). 15,230 reflections collected, 2807 independent reflections with I>2s(I) (2qmax¼29.18 ), and 162 parameters were used for the solution of the structure. The non-hydrogen atoms were refined anisotropically. R1¼0.0446 and wR2¼0.1271, GOF¼1.061. Crystallographic data (excluding structure factors) for the structure reported in this paper have been deposited with the Cambridge Crystallographic Data Center as supplementary publication no. CCDC-769543 for ()-15. Copies of the data can be obtained free of charge on application to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK [fax: int. code þ44 1223 336 033; e-mail: [email protected]]. 4.8. Epoxidation of (D)-6a to (L)-15 with in situ-generated peracid from UHP and Ac2O (Scheme 8)14 To a stirred mixture of urea hydrogen peroxide (47 mg, 0.5 mmol), sodium hydrogen phosphate (62.5 mg, 0.44 mmol) and (þ)-6a (92% ee; 10.8 mg, 0.05 mmol) in CH2Cl2 (0.5 mL) was added acetic anhydride (24 mL, 0.25 mmol) dropwise at 0  C. The resulting mixture was allowed to warm to room temperature and stirred for additional 3 days. The resulting mixture was diluted with CHCl3 and washed with brine. The aqueous layer was extracted with CHCl3, and the combined organic layers were dried over anhydrous Na2SO4 and solvents were removed in

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M. Uyanik et al. / Tetrahedron 66 (2010) 5841e5851

vacuo. The conversion (52%) of 6a to epoxyspirolactones and the diastereomeric ratio (92:8) were determined by 1H NMR analysis of the crude mixture. The residue was purified by flash column chromatography on silica gel (eluent: hexaneeEtOAc¼5:1) to give ()-15 (92% ee; 5.4 mg, 0.024 mmol) as a single compound in 47% yield.

m/z calcd for C13H11O4 (MþH) 231.0657, found 231.0659; HPLC (ODH column), hexaneeiPrOH¼85:15 as eluent, 1.0 mL/min, tR¼24.9 min (major), 28.1 min (minor); [a]24 D þ197.7 (c 0.8, CHCl3) for 92% ee.

4.9. Re-catalyzed epoxidation of (D)-6a to (L)-15 with H2O2 (Scheme 8)15

Financial support for this project was provided by JSPS.KAKENHI (20245022), NEDO, the Shionogi Award in Synthetic Organic Chemistry, Japan, the Nitto Foundation, and the Global COE Program of MEXT.

To a solution of (þ)-6a (92% ee; 21.4 mg, 0.1 mmol), MeReO3 (5

mg, 2 mmol) and 3-cyanopyridine (4.2 mg, 0.04 mmol) in CH2Cl2 (0.25 mL) was added slowly 30 wt % H2O2 (41.2 mL, 0.4 mmol) at

room temperature. After stirring for 48 h at ambient temperature, the resulting mixture was diluted with CHCl3 and washed with brine. The aqueous layer was extracted with EtOAc, and the combined organic layers were dried over anhydrous Na2SO4 and solvents were removed in vacuo. The conversion (88%) of 6a to epoxyspirolactones and the diastereomeric ratio (92:8) were determined by 1H NMR analysis of the crude mixture. The residue was purified by flash column chromatography on silica gel (eluent: hexaneeEtOAc¼5:1) to give ()-15 (92% ee; 16.0 mg, 0.07 mmol) in 70% yield. 4.10. Oxidation of (D)-6a with NBS to bromohydrin spirolactone (D)-17 16 To a solution of (þ)-6a (92% ee; 10.7 mg, 0.05 mmol) in THF (0.25 mL) was added water (0.25 mL) at 0  C until the solution became cloudy. NBS (recrystallized, 17.8 g, 0.10 mmol) was then added and the reaction was allowed to stir for 28 h at 0  C. The resulting mixture was diluted with EtOAc and washed with brine. The aqueous layer was extracted with EtOAc, and the combined organic layers were dried over anhydrous Na2SO4 and solvents were removed in vacuo. The residue was purified by flash column chromatography on silica gel (eluent: hexaneeEtOAc¼10:1 to 4:1) to give (þ)-16 (92% ee; 10.9 mg, 0.035 mmol) in 70% yield. White amorphous; TLC, Rf¼0.20 (hexaneeEtOAc¼1:1); IR (film) 1793, 1699, 1602, 1456, 1210, 1175 cm1; 1H NMR (CDCl3, 400 MHz) d 2.39e2.47 (m, 1H), 2.81e2.86 (m, 2H), 3.01 (d, J¼4.1 Hz, 1H), 3.09e3.17 (m, 1H), 4.47 (d, J¼9.2 Hz, 1H), 5.33 (dd, J¼4.1, 9.2 Hz, 1H), 7.51 (t, J¼7.8 Hz, 1H), 7.73 (t, J¼7.8 Hz, 1H), 7.81 (d, J¼7.8 Hz, 1H), 8.07 (d, J¼7.8 Hz, 1H); 13C NMR (CDCl3, 100 MHz) d 27.5, 28.5, 63.3, 70.1, 86.1, 127.4, 128.2, 128.4, 129.0, 135.7, 142.1, 175.5 188.5; HRMS (FABþ) m/z calcd for C13H12BrO4 (MþH) 310.9919, found 310.9926; HPLC (OD-H column), hexaneeEtOH¼4:1 as eluent, 1.0 mL/min, tR¼8.6 min (major), 9.7 min (minor); [a]22 D þ137.8 (c 0.6, CHCl3) for 92% ee. 4.11. Conversion of bromohydrin (D)-17 to epoxyspirolactone (D)-16 (Scheme 9) To a solution of (þ)-17 (92% ee; 12.4 mg, 0.04 mmol) in acetone (0.8 mL) was added K2CO3 (13.8 mg, 0.1 mmol) at room temperature, and the resulting mixture was stirred for 21 h at ambient temperature. The resulting mixture was filtered through Celite, and the solvents were removed in vacuo. The residue was purified by flash column chromatography on silica gel (eluent: hexaneeEtOAc¼10:1 to 4:1) to give (þ)-16 (92% ee; 9.1 mg, 0.04 mmol) in >99% yield. White solid; TLC, Rf¼0.34 (hexaneeEtOAc¼1:1); IR (film) 3028, 1795, 1698, 1605, 1303, 1185 cm1; 1H NMR (CDCl3, 400 MHz) d 2.43e2.49 (m, 1H), 2.71e2.80 (m, 1H), 2.95e3.06 (m, 2H), 3.93 (d, J¼3.7 Hz, 1H), 4.17 (d, J¼3.7 Hz, 1H), 7.54 (t, J¼7.8 Hz, 1H), 7.62e7.70 (m, 2H), 7.99 (d, J¼7.8 Hz, 1H); 13C NMR (CDCl3, 100 MHz) d 27.7, 28.4, 52.7, 57.8, 80.7, 129.0, 129.6, 130.0 (2C), 134.4, 137.7, 175.6, 190.6; HRMS (FABþ)

Acknowledgements

Supplementary data Supplementary data associated with this article can be found in online version at doi:10.1016/j.tet.2010.04.060. These data include MOL files and InChIKeys of the most important compounds described in this article. References and notes 1. For recent reviews focused on hypervalent iodine chemistry, see: (a) Hypervalent Iodine Chemistry; Wirth, T., Ed.Top. Curr. Chem.; Springer: Berlin, 2003; Vol. 224; (b) Wirth, T. Organic Synthesis Highlights V; Wiley-VCH: Weinheim, 2003; p 144; (c) Ciufolini, M. A.; Braun, N. A.; Canesi, S.; Ousmer, M.; Chang, J.; Chai, D. Synthesis 2007, 3759e3772; (d) Quideau, S.; Pouysegu, L.; Deffieux, D. Synlett 2008, 467e495; (e) Zhdankin, V. V.; Stang, P. J. Chem. Rev. 2008, 108, 5299e5358; (f) Pouységu, L.; Deffieux, D.; Quideau, S. Tetrahedron 2010, 66, 2235e2261. 2. For reviews focused on hypervalent iodine-catalyzed oxidation reactions, see: (a) Richardson, R. D.; Wirth, T. Angew. Chem., Int. Ed. 2006, 45, 4402e4404; (b) Ochiai, M.; Miyamoto, K. Eur. J. Org. Chem. 2008, 4229e4239; (c) Dohi, T.; Kita, Y. Chem. Commun. 2009, 2073e2085; (d) Uyanik, M.; Ishihara, K. Chem. Commun. 2009, 2086e2099; For our recent contributions, see: (e) Uyanik, M.; Yasui, T.; Ishihara, K. Bioorg. Med. Chem. Lett. 2009, 48, 3848e3851; (f) Uyanik, M.; Akakura, M.; Ishihara, K. J. Am. Chem. Soc. 2009, 131, 251e262; (g) Uyanik, M.; Fukatsu, R.; Ishihara, K. Org. Lett. 2009, 11, 3470e3473. 3. For the stoichiometric use of the chiral hypervalent iodines, see: (a) Up to 53% ee: Imamoto, T.; Koto, H. Chem. Lett. 1986, 15, 967e968; (b) Up to 56% ee: Ray, D. G., III; Koser, G. F. J. Am. Chem. Soc. 1990, 112, 5672e5673; (c) Up to 53% ee: Ochiai, M.; Takaoka, Y.; Masaki, Y. J. Am. Chem. Soc. 1999, 121, 9233e9234; (d) Up to 72% ee: Tohma, H.; Takizawa, S.; Watanabe, H.; Fukuoka, Y.; Maegawa, T.; Kita, Y. J. Org. Chem. 1999, 64, 3519e3523; (e) Up to 65% ee: Hirt, U. H.; Schuster, M. F. H.; French, A. N.; Wiest, O. G.; Wirth, T. Eur. J. Org. Chem. 2001, 1569e1579; (f) Up to 41% ee: Ladziata, U.; Carlson, J.; Zhdankin, V. V. Tetrahedron Lett. 2006, 47, 6301e6304; (g) Up to 64% ee: Fujita, M.; Okuno, S.; Lee, H. J.; Sugimura, T.; Okuyama, T. Tetrahedron Lett. 2007, 48, 8691e8694; (h) Up to 77% ee: Boppisetti, J. K.; Birman, V. B. Org. Lett. 2009, 11, 1221e1223; (i) Up to 50% ee: Quideau, S.; Lyvinec, G.; Marguerit, M.; Bathany, K.; Ozanne-Beaudenon, A.; Buffeteau, T.; Cavagnat, D.; Chenede, A. Angew. Chem., Int. Ed. 2009, 48, 4605e4609. 4. For the catalytic use of the chiral hypervalent iodines generated in situ, see: (a) Up to 44% ee: Altermann, S. M.; Richardson, R. D.; Page, T. K.; Schmidt, R. K.; Holland, E.; Mohammed, U.; Paradine, S. M.; French, A. N.; Richter, C.; Bahar, A. M.; Witulski, B.; Wirth, T. Eur. J. Org. Chem. 2008, 5315e5328; (b) Up to 29% ee: Ref. 3i. 5. For the first use of mCPBA as co-oxidant for the in situ generation of hypervalent iodine compounds, see: (a) Tohma, H.; Maruyama, A.; Maeda, A.; Maegawa, T.; Dohi, T.; Shiro, M.; Morita, T.; Kita, Y. Angew. Chem., Int. Ed. 2004, 43, 3595e3598; (b) Ochiai, M.; Takeuchi, Y.; Katayama, T.; Sueda, T.; Miyamoto, K. J. Am. Chem. Soc. 2005, 127, 12244e12245; (c) Dohi, T.; Maruyama, A.; Yoshimura, M.; Morimoto, K.; Tohma, H.; Kita, Y. Angew. Chem., Int. Ed. 2005, 44, 6193e6196. 6. (a) Dohi, T.; Maruyama, A.; Takenaga, N.; Senami, K.; Minamitsuji, Y.; Fujioka, H.; Caemmerer, S. B.; Kita, Y. Angew. Chem., Int. Ed. 2008, 47, 3787e3790; (b) Dohi, T.; Kita, Y.; Maruyama, A. Jpn. Kokai Tokkyo Koho 2009149564-A. 7. Uyanik, M.; Yasui, T.; Ishihara, K. Angew. Chem., Int. Ed. 2010, 49, 2175e2177. 8. We do not yet have any experimental proof of the non-bonding interactions between the iodine(III)-center and functional groups in 8. However, there are many reports on the intra- or intermolecular secondary interactions of iodine (III and V). For selected examples, see: (a) Zhdankin, V. V.; Koposov, A. E.; Smart, J. T. J. Am. Chem. Soc. 2001, 123, 4095e4096; (b) Ochiai, M. Coord. Chem. Rev. 2006, 250, 2771e2781 and references therein. 9. Compound 9 was easily prepared from resorcinol, see: Tsujiyama, S.; Suzuki, K.; Guthrie, D. B.; Gibney, H. M.; Curran, D. P. Org. Synth. 2007, 84, 272e284. 10. Kitani, Y.; Morita, A.; Kumamoto, T.; Ishikawa, T. Helv. Chim. Acta 2002, 85, 1186e1195. 11. Kita and co-workers also reported that enantiomerically pure 6d was obtained after a single recrystallization, see: Ref. 6b.

M. Uyanik et al. / Tetrahedron 66 (2010) 5841e5851 12. (a) Cox, C.; Danishefsky, S. J. Org. Lett. 2001, 3, 2899e2902; (b) Siu, T.; Cox, C. D.; Danishefsky, S. J. Angew. Chem., Int. Ed. 2003, 42, 5629e5634. 13. For similar one-pot oxidation using mCPBA, see: (a) Ref. 3i; For epoxidation of a-tetralone-derived alkene with mCPBA, see: (b) Coogan, M. P.; Haigh, R.; Hall, A.; Harris, L. D.; Hibbs, D. E.; Jenkins, R. L.; Jones, C. L.; Tomkinson, N. C. O. Tetrahedron 2003, 59, 7389e7395.

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